The mammary gland has a natural ability to prevent bacterial invasion, but various physiological events can inhibit this capability. For example, the ability of mammary gland neutrophils to phagocytize mastitis-causing pathogens and suppress bacterial multiplication is critical to, the outcome of intramammary infection (Paape et al., 1979). Although both neutrophils and macrophages predominate in mammary secretions and tissues (Sordillo et al., 1987; Sordillo and Nickerson, 1988), evidence suggests that the antibacterial activities of these cells are reduced in the presence of mammary secretions and compromised during physiological transitions of the gland (Paape et al., 1981; Nagahata et al., 1988; Sordillo and Nickerson, 1988). Consequently, the bovine mammary gland is highly susceptible to mastitis immediately following the cessation of lactation and during the periparturient period (Nickerson, 1989). Incidence of clinical mastitis is highest during early lactation often resulting from new intramammary infections obtained during the nonlactating period. Increased susceptibility during these times is most likely due to a combination of increased exposure of teat ends to mastitis-causing pathogens and diminished host defense mechanisms, as described above, during functional transitions of the mammary gland.
Mastitis during the periparturient and early lactating periods is caused by a multitude of bacteria. Common etiological agents include Escherichia coli and Staphylococcus sp. Coliform infection is rare in middle and late lactation, but is most severe during the first few weeks of lactation where it is a major cause of acute toxic mastitis. Disparities in establishment and severity of, coliform mastitis with respect to stage of lactation have been explained by the rate of growth of the organism within the gland, the elaboration and absorption of toxins, and the varying susceptibility of the host during these stages. A rapid and intense inflammatory response in lactating tissue has been observed following experimental challenge with E. coli (Hill, 1981). In most cases, the bacteria were eliminated rapidly without causing damage to secretory parenchymal tissue. In contrast, quarters infected with E. coli during the immediate postpartum period had minimal neutrophil influx, which probably allows the unrestricted growth of the organism. The delayed diapedesis of neutrophils and slow inflammatory response within the gland may be a result of decreased sensitivity of alveolar and ductular epithelium to endotoxins during functional transitions of the gland.
Interferons (IFN) are a family of closely related proteins of three major types (Lawman et al., 1989). Interferons-alpha and -beta are produced by a variety of cell types in response to several inducers including viral infections, bacterial products and tumor cells. Interferon-gamma is predominantly produced by antigen- or mitogen-stimulated T-lymphocytes. In addition to the antiviral and antiproliferative activities, all classes of IFN are known to exhibit many immunomodulatory properties (Lawman et al., 1989).
IFN-gamma has been shown to be a potent immunomodulator and appears to enhance natural killer cell activity, antibody-dependent cellular cytotoxicity, and cytotoxic T-lymphocyte activity (Lawman et al., 1989). Interferon-gamma also enhances macrophage-mediated cytotoxicity against tumor cells, induces membrane-bound Fc receptors for IgG on macrophages, and stimulates the synthesis and release of reactive oxygen metabolites from both macrophages and neutrophils (Bielefeldt Ohmann and Babiuk, 1986; Trinchieri and Perussia, 1985).
The efficacy of interferons in the treatment of mastitis has not heretofore been studied to applicants' knowledge.